title: Distinct functional regions of the human polymeric immunoglobulin receptor.
abstract: The polymeric immunoglobulin receptor (pIgR) is a type I transmembrane protein that is expressed on the surfaces of glandular and intestinal epithelial cells. The extracellular portion of the pIgR is composed of six different domains. Domain 6 is involved in the enzymatic cleavage and release of the pIgR into the intestinal lumen as a free secretory component (fSC). A highly conserved 9-amino acid sequence is present in this region in various species. Although mutations in domain 6 are associated with particular diseases, such as IgA nephropathy and Epstein-Barr virus-related nasopharyngeal cancer, and the glutamic acid residues in the conserved 9-amino acid sequence are expected to be indispensable for the secretion of fSC, the importance of these residues has not been examined. In the present study, we attempted to examine the role of these residues in the enzymatic cleavage of the pIgR. The enzymatic cleavage of the pIgR was not affected by the presence of an alanine to valine substitution at position 580 or glutamine to alanine substitutions at positions 606 and/or 607, or the deletion of the whole 9-amino acid conserved sequence. Intriguingly, the 10 amino acid sequences flanking the N- and C-terminal ends of the conserved 9-amino acid sequence had opposite effects on pIgR cleavage. Namely, the N-terminal and C-terminal sequences enhanced and reduced pIgR cleavage efficiency, respectively. These results indicated that the pIgR can be divided into several functionally distinct regions.
authors.affiliation: Department of Pathology, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sunagawa
authors.forename: D
authors.initials: D
authors.lastname: Omagari
authors.forename: M
authors.initials: M
authors.lastname: Nishiyama
authors.forename: M
authors.initials: M
authors.lastname: Asano
authors.forename: M
authors.initials: M
authors.lastname: Okudera
authors.forename: M
authors.initials: M
authors.lastname: Sugitani
authors.forename: N
authors.initials: N
authors.lastname: Nemoto
authors.forename: K
authors.initials: K
authors.lastname: Komiyama
mesh_terms: D000409:Alanine / Q000235:genetics; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005973:Glutamine / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics* / Q000378:metabolism; D019056:Receptors, Polymeric Immunoglobulin / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D014162:Transfection; D014633:Valine / Q000235:genetics
chemical_list: D050505:Mutant Proteins; D019056:Receptors, Polymeric Immunoglobulin; D005973:Glutamine; D014633:Valine; D000409:Alanine